Yonsei Med J.  2007 Aug;48(4):573-585. 10.3349/ymj.2007.48.4.573.

Mucocutaneous Lesions of Behcet's Disease

• Alpsoy E
• Zouboulis
• Ehrlich GE

• KMID: 2158161
• DOI: http://doi.org/10.3349/ymj.2007.48.4.573

Abstract

Behcet's disease is particularly prevalent in "Silk Route" populations, but it has a global distribution. The diagnosis of the disease is based on clinical criteria as there is as yet no pathognomonic test, and mucocutaneous lesions, which figure prominently in the presentation and diagnosis, may be considered the diagnostic hallmarks. Among the internationally accepted criteria, painful oral and genital ulcers, cutaneous vasculitic lesions and reactivity of the skin to needle prick or injection (the pathergy reaction) are considered hallmarks of Behcet's disease, and often precede other manifestations. Their recognition may permit earlier diagnosis and treatment, with salutary results. This paper describes the various lesions that constitute the syndrome and focuses on those that may be considered characteristic.

Keyword

Behcet's disease; mucocutaneous lesions; treatment; review

MeSH Terms

Behcet Syndrome/drug therapy/*pathology
Female
Humans
Male
Oral Ulcer/drug therapy/pathology
Skin Ulcer/drug therapy/pathology
Thrombophlebitis/drug therapy/pathology

Figure

• 

  Fig. 1 Clinical photograph showing multiple oral ulcers of Behçet's disease with grayish yellow necrotic base and erythematous surrounds on the lower lip mucosa.

• 

  Fig. 2 Oral ulcer on the lateral side of the tongue with rolled borders and yellow necrotic base.

• 

  Fig. 3 Genital ulcer on the scrotum which is the most frequently involved site in male patients.

• 

  Fig. 4 Genital ulcer together with a pustule on the vestibule in a female patient.

• 

  Fig. 5 Several papulopustular lesions on erythematous base on the trunk.

• 

  Fig. 6 Erythema nodosum-like lesions; tender, 1 to 3 cm, erythematous nodules on the lower extremities in a female patient.

• 

  Fig. 7 Superficial thrombophlebitis with erythematous, tender, subcutaneous nodules arranged in a linear fashion in a male patient.

• 

  Fig. 8 Extragenital ulceration resembling aphthous lesions of the disease in the axillae region.

• 

  Fig. 9 The skin pathergy test positivity is defined as at least a papule or pustule on an erythematous base observed at the needle-prick site 48 hours after application of a sterile needle that penetrated to the corium of an avascular site on the forearm.

• 

  Fig. 10 Acral purpuric papulonodular lesion in a female patient with Behçet's disease.

Reference

1. Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med. 1999. 341:1284–1291.

2. Ehrlich GE, Kajani M, Schwartz IR, McAlack RF. Further studies of platelet rosettes around granulocytes in Behçet's syndrome. Inflammation. 1975. 1:223–225.

3. Lehner T. Immunopathogenesis of Behçet's disease. Ann Med Interne (Paris). 1999. 150:483–487.

4. Alpsoy E, Yılmaz E, Coşkun M, Savaş A, Yeğin O. HLA antigens and linkage disequilibrium patterns in Turkish Behçet's patients. J Dermatol. 1998. 25:158–162.

5. Alpsoy E, Çayırlı C, Er H, Yılmaz E. The levels of plasma interleukin-2 and soluble interleukin-2R in Behçet's disease: as a marker of disease activity. J Dermatol. 1998. 25:513–516.

6. International Study Group for Behçet's Disease. Criteria for diagnosis of Behçet's disease. Lancet. 1990. 335:1078–1080.

7. O'Neill TW, Rigby AS, Silman AJ, Barnes C. Validation of the International Study Group criteria for Behçet's disease. Br J Rheumatol. 1994. 33:115–117.

8. Zouboulis CC. Epidemiology of Adamantiades-Behçet's disease. Ann Med Interne (Paris). 1999. 150:488–498.

9. Zouboulis CC, Kotter I, Djawari D, Kirch W, Kohl PK, Ochsendorf FR, et al. Lee S, Bang D, Lee E-S, Sohn S, editors. Adamantiades-Behçet's disease: Epidemiology in Germany and in Europe. Behçet's Disease. A Guide to its Clinical Understanding. Textbook and Atlas. 2001. Berlin, Heidelberg: Springer;157–169.

10. Müftüoğlu AU, Yazıcı H, Yurdakul S, Pazarlı H, Ozyazgan Y, Tüzün Y, et al. Behçet's disease: lack of correlation of clinical manifestations with HLA antigens. Tissue Antigens. 1981. 17:226–230.

11. Yamamoto S, Toyokawa H, Matsubara J, Yanai H, Inaba Y, Nakae K. A nation-wide survey of Behçet's disease in Japan. 1. Epidemiological survey. Jpn J Ophthalmol. 1974. 18:282–290.

12. Saylan T, Ozarmağan G, Azizlerli G, Ovül C, Oke N. Behçet disease in Türkey. Z Hautkr. 1986. 61:1120–1122.

13. Gürler A, Boyvat A, Türsen U. Clinical manifestations of Behçet's disease: an analysis of 2147 patients. Yonsei Med J. 1997. 38:423–427.

14. Zouboulis CC, Kötter I, Djawari D, Kirch W, Kohl PK, Ochsendorf FR, et al. Epidemiological features of Adamantiades-Behçet's disease in Germany and in Europe. Yonsei Med J. 1997. 38:411–422.

15. Durusoy C, Alpsoy E, Elpek GO, Karpuzoğlu G. Histological findings and androgen receptor levels in the sebaceous glands of papulopustular lesions from patients with Behçet's disease and acne vulgaris: A Controlled Study. Adv Clin Path. 2002. 6:87–93.

16. Yazıcı H, Tüzün Y, Pazarlı H, Yurdakul S, Ozyazgan Y, Ozdoğan H, et al. Influence of age of onset and patient's sex on the prevalence and severity of manifestations of Behçet's syndrome. Ann Rheum Dis. 1984. 3:783–789.

17. Demiroğlu H, Barışta İ, Dündar S. Risk factor assessment and prognosis of eye involvement in Behçet's disease in Turkey. Ophthalmology. 1997. 104:701–705.

18. Yazıcı H, Başaran G, Hamuryudan V, Hızlı N, Yurdakul S, Mat C, et al. The ten-year mortality in Behçet's syndrome. Br J Rheumatol. 1996. 35:139–141.

19. Alpsoy E, Dönmez L, Bacanlı A, Apaydın C, Butun B. Review of the chronology of clinical manifestations in 60 patients with Behçet's disease. Dermatology. 2003. 207:354–356.

20. Alpsoy E, Aktekin M, Er H, Durusoy Ç, Yılmaz E. A randomized, controlled and blinded study of papulopustular lesions in Turkish Behçet's patients. Int J Dermatol. 1998. 37:839–843.

21. Alpsoy E, Er H, Durusoy Ç, Yılmaz E. The use of sucralfate suspension in the treatment of oral and genital ulceration of Behçet disease: a randomized, placebo-controlled, double-blind study. Arch Dermatol. 1999. 135:529–532.

22. Main DM, Chamberlain MA. Clinical differentiation of oral ulceration in Behçet's disease. Br J Rheumatol. 1992. 31:767–770.

23. Bang D, Yoon KH, Chung HG, Choi EH, Lee ES, Lee S. Epidemiological and clinical features of Behçet's disease in Korea. Yonsei Med J. 1997. 38:428–436.

24. Ghate JV, Jorizzo JL. Behçet's disease and complex aphthosis. J Am Acad Dermatol. 1999. 40:1–18.

25. Schreiner DT, Jorizzo JL. Behçet's disease and complex aphthosis. Dermatol Clin. 1987. 5:769–778.

26. Chajek T, Fainaru M. Behçet's disease. Report of 41 cases and a review of the literature. Medicine (Baltimore). 1975. 54:179–196.

27. Alpsoy E, Durusoy Ç, Yılmaz E, Özgürel Y, Ermiş O, Yazar Ş, Başaran E. Interferon alpha-2a in the treatment of Behçet disease: a randomized, placebo-controlled and double-blind study. Arch Dermatol. 2002. 138:467–471.

28. Greenberg MS. HIV-associated lesions. Dermatol Clin. 1996. 14:319–326.

29. Jorizzo JL, Taylor RS, Schmalstieg FC, Solomon AR, Daniels JC, Rudloff HE, et al. Complex aphthosis: a forme fruste of Behçet's syndrome? J Am Acad Dermatol. 1985. 13:80–84.

30. Arbesfeld SJ, Kurban AK. Behçet's disease. New perspectives on an enigmatic syndrome. J Am Acad Dermatol. 1988. 19:767–779.

31. Stratigos AJ, Laskaris G, Stratigos JD. Behçet's disease. Semin Neurol. 1992. 12:346–357.

32. Ergun T, Gürbüz O, Doğusoy G, Mat C, Yazıcı H. Histopathologic features of the spontaneous pustular lesions of Behçet's syndrome. Int J Dermatol. 1998. 37:194–196.

33. Jorizzo JL, Abernethy JL, White WL, Mangelsdorf HC, Zouboulis CC, Sarica R, et al. Mucocutaneous criteria for the diagnosis of Behçet's disease: an analysis of clinicopathologic data from multiple international centers. J Am Acad Dermatol. 1995. 32:968–976.

34. Alpsoy E, Uzun S, Akman A, Acar MA, Memişoğlu HR, Başaran E. Histologic and immunofluorescence findings of non-follicular papulopustular lesions in patients with Behçet's disease. J Eur Acad Dermatol Venereol. 2003. 17:521–524.

35. Kim B, LeBoit PE. Histopathologic features of erythema nodosum-like lesions in Behçet disease: a comparison with erythema nodosum focusing on the role of vasculitis. Am J Dermatopathol. 2000. 22:379–390.

36. Chun SI, Su WP, Lee S, Rogers RS. Erythema nodosum-like lesions in Behçet's syndrome: a histopathologic study of 30 cases. J Cutan Pathol. 1989. 16:259–265.

37. Koç Y, Güllü I, Akpek G, Akpolat T, Kansu E, Kiraz S, et al. Vascular involvement in Behçet's disease. J Rheumatol. 1992. 19:402–410.

38. Kansu E, Özer FL, Akalın E, Güler Y, Zileli T, Tanman E, et al. Behçet's syndrome with obstruction of the venae cavae. A report of seven cases. Q J Med. 1972. 41:151–168.

39. Demircioğlu FF, Böke E, Demircin M, Dağsalı S, Küçükali T. Abdominal aortic aneurysm with inferior vena cava obstruction: case report. Angiology. 1989. 40:227–232.

40. Azizlerli G, Ozarmağan G, Ovül C, Sarıca R, Mustafa SO. A new kind of skin lesion in Behçet's disease: extragenital ulcerations. Acta Derm Venereol. 1992. 72:286.

41. Krüger K, Fritz K, Daniel V, Zouboulis CC. Juvenile Adamantiades-Behçet disease in decreased stimulation with anti-CD3 monoclonal antibody. Hautarzt. 1997. 48:258–261.

42. Treudler R, Orfanos CE, Zouboulis CC. Twenty-eight cases of juvenile-onset Adamantiades-Behçet disease in Germany. Dermatology. 1999. 199:15–19.

43. Altaç M, Tüzün Y, Yurdakul S, Binyıldız P, Yazıcı H. The validity of the pathergy test (non-specific skin hyperreactivity) in Behçet's disease: a double-blind study by independent observers. Acta Derm Venereol. 1982. 62:158–159.

44. Ergun T, Gürbüz O, Harvell J, Jorizzo J, White W. The histopathology of pathergy: a chronologic study of skin hyperreactivity in Behçet's disease. Int J Dermatol. 1998. 37:929–933.

45. Jorizzo JL, Solomon AR, Cavallo T. Behçet's syndrome. Immunopathologic and histopathologic assessment of pathergy lesions is useful in diagnosis and follow-up. Arch Pathol Lab Med. 1985. 109:747–751.

46. Fresko I, Yazıcı H, Bayramiçli M, Yurdakul S, Mat C. Effect of surgical cleaning of the skin on the pathergy phenomenon in Behçet's syndrome. Ann Rheum Dis. 1993. 52:619–620.

47. Oğuz O, Serdaroğlu S, Tüzün Y, Erdoğan N, Yazıcı H, Savaşkan H. Acute febrile neutrophilic dermatosis (Sweet's syndrome) associated with Behçet's disease. Int J Dermatol. 1992. 31:645–646.

48. Cho KH, Shin KS, Sohn SJ, Choi SJ, Lee YS. Behçet's disease with Sweet's syndrome-like presentation-a report of six cases. Clin Exp Dermatol. 1989. 14:20–24.

49. Armas JB, Davies J, Davis M, Lovell C, McHugh N. Atypical Behçet's disease with peripheral erosive arthropathy and pyoderma gangrenosum. Clin Exp Rheumatol. 1992. 10:177–180.

50. Lee ES, Bang D, Lee S. Dermatologic manifestation of Behçet's disease. Yonsei Med J. 1997. 38:380–389.

51. Golan G, Beeri R, Mevorach D. Henoch-Schonlein purpura-like disease representing a flare of Behçet's disease. Br J Rheumatol. 1994. 33:1198–1199.

52. Cornelis F, Sigal-Nahum M, Gaulier A, Bleichner G, Sigal S. Behçet's disease with severe cutaneous necrotizing vasculitis: response to plasma exchange-report of a case. J Am Acad Dermatol. 1989. 21:576–579.

53. Cantini F, Salvarani C, Niccoli L, Senesi C, Truglia MC, Padula A, et al. Behçet's disease with unusual cutaneous lesions. J Rheumatol. 1998. 25:2469–2472.

54. Liao YH, Hsiao GH, Hsiao CH. Behçet's disease with cutaneous changes resembling polyarteritis nodosa. Br J Dermatol. 1999. 140:368–369.

55. King R, Crowson AN, Murray E, Magro CM. Acral purpuric papulonodular lesions as a manifestation of Behçet's disease. Int J Dermatol. 1995. 34:190–192.

56. Kienbaum S, Zouboulis CC, Waibel M, Orfanos CE. Wechsler B, Godeau P, editors. Chemotactic neutrophilic vasculitis: a new histopathological pattern of vasculitis found in mucocutaneous lesions of patients with Adamantiades-Behçet's disease. Behçet's disease. 1993. Amsterdam London New York Tokyo: Excerpta Medica;337–341. International Congress Series 1037.

57. Lakhanpal S, Tani K, Lie JT, Katoh K, Ishigatsubo Y, Ohokubo T. Pathologic features of Behçet's syndrome: a review of Japanese autopsy registry data. Hum Pathol. 1985. 16:790–795.

58. Kienbaum S, Zouboulis ChC, Waibel M, Orfanos CE. Wechsler B, Godeau P, editors. Papulopustular skin lesions in Adamantiades-Behçet's disease show a similar histopathological pattern as the classical mucocutaneous manifestations. Behçet's disease. 1993. Amsterdam London New York Tokyo: Excerpta Medica;331–336. International Congress Series 1037.

59. Zouboulis CC, Katsantonis J, Ketteler R, Treudler R, Kaklamani E, Hornemann S, et al. Adamantiades-Behçet's disease: Interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells. Arch Dermatol Res. 2000. 292:279–284.

60. Treudler R, Zouboulis CC, Bttner P, Detmar M, Orfanos CE. Enhanced interaction of patients' lymphocytes with human dermal microvascular endothelial cell cultures in active Adamantiades-Behçet disease. Arch Dermatol. 1996. 132:1323–1329.

61. Zouboulis CC, Kurz K, Bratzke B, Orfanos CE. Adamantiades-Behçet disease: necrotizing systemic vasculitis with a fatal outcome. Hautarzt. 1991. 42:451–454.

62. Gamble CN, Wiesner KB, Shapiro RF, Boyer WJ. The immune complex pathogenesis of glomerulonephritis and pulmonary vasculitis in Behçet's disease. Am J Med. 1979. 66:1031–1039.

63. Jorizzo JL, Hudson RD, Schmalstieg FC, Daniels JC, Apisarnthanarax P, Henry JC, et al. Behçet's syndrome: immune regulation, circulating immune complexes, neutrophil migration, and colchicine therapy. J Am Acad Dermatol. 1984. 10:205–214.

64. Hay D, Reade PC. The use of an elimination diet in the treatment of recurrent aphthous ulceration of the oral cavity. Oral Surg Oral Med Oral Pathol. 1984. 57:504–507.

65. Greer RO, Lindenmuth JE, Juarez T, Khandwala A. A double-blind study of topically applied 5% amlexanox in the treatment of aphthous ulcers. J Oral Maxillofac Surg. 1993. 51:243–249.

66. Matthews RW, Scully CM, Levers BG, Hislop WS. Clinical evaluation of benzydamine, chlorhexidine, and placebo mouthwashes in the management of recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol. 1987. 63:189–191.

67. Graykowski EA, Kingman A. Double-blind trial of tetracycline in recurrent aphthous ulceration. J Oral Pathol. 1978. 7:376–382.

68. Collier PM, Neill SM, Copeman PW. Topical 5-aminosalicylic acid: a treatment for aphthous ulcers. Br J Dermatol. 1992. 126:185–188.

69. Hamuryudan V, Özyazgan Y, Hızlı N, Mat C, Yurdakul S, Tüzün Y, et al. Azathioprine in Behçet's syndrome: effects on long-term prognosis. Arthritis Rheum. 1997. 40:769–774.

70. Simsek H, Dundar S, Telatar H. Treatment of Behçet's disease with indomethacin. Int J Dermatol. 1991. 30:54–57.

71. Yasui K, Ohta K, Kobayashi M, Aizawa T, Komiyama A. Successful treatment of Behçet's disease with pentoxifylline. Ann Intern Med. 1996. 124:891–893.

72. Chandrasekhar J, Liem AA, Cox NH, Paterson AW. Oxypentifylline in the management of recurrent aphthous oral ulcers: an open clinical trial. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999. 87:564–567.

73. Yurdakul S, Mat C, Tüzün Y, Ozyazgan Y, Hamuryudan V, Uysal O, et al. A double-blind trial of colchicine in Behçet's syndrome. Arthritis Rheum. 2001. 44:2686–2692.

74. Sharquie KE. Suppression of Behçet's disease with dapsone. Br J Dermatol. 1984. 110:493–494.

75. Zouboulis CC, Orfanos CE. Treatment of Adamantiades-Behçet disease with systemic interferon alfa. Arch Dermatol. 1998. 134:1010–1016.

76. Katsantonis J, Seltmann H, Wrobel A, Adler YD, Hornemann S, Orfanos CE, et al. In : Bang D, Lee E-S, Lee S, editors. Xenobiotic regulation of endothelial intracellular and secreted interleukin-8 induced by serum of patients with Adamantiades-Behçet's disease. Behçet's Disease. 2001. Proceedings of the 9th International Conference on Behçet's Disease and the 8th International Conference on Behçet's Disease; >Seoul: Library of Congress Cataloging;236–239.

77. Yazıcı H, Pazarlı H, Barnes CG, Tüzün Y, Ozyazgan Y, Silman A, et al. A controlled trial of azathioprine in Behçet's syndrome. N Engl J Med. 1990. 322:281–285.

78. Avcı O, Gürler N, Güneş AT. Efficacy of cyclosporine on mucocutaneous manifestations of Behçet's disease. J Am Acad Dermatol. 1997. 36:796–797.

79. Jorizzo JL, White WL, Wise CM, Zanolli MD, Sherertz EF. Low-dose weekly methotrexate for unusual neutrophilic vascular reactions: cutaneous polyarteritis nodosa and Behçet's disease. J Am Acad Dermatol. 1991. 24:973–978.

80. Jorizzo JL, Schmalstieg FC, Solomon AR, Cavallo T, Taylor RS, Rudloff HB, et al. Thalidomide effects in Behçet's syndrome and pustular vasculitis. Arch Intern Med. 1986. 146:878–881.

81. Hamuryudan V, Mat C, Saip S, Ozyazgan Y, Siva A, Yurdakul S, et al. Thalidomide in the treatment of the mucocutaneous lesions of the Behçet syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998. 128:443–450.

82. Goossens PH, Verburg RJ, Breedveld FC. Remission of Behçet's syndrome with tumour necrosis factor alpha blocking therapy. Ann Rheum Dis. 2001. 60:637.

83. Travis SP, Czajkowski M, McGovern DP, Watson RG, Bell AL. Treatment of intestinal Behçet's syndrome with chimeric tumour necrosis factor alpha antibody. Gut. 2001. 49:725–728.

84. Robertson LP, Hickling P. Treatment of recalcitrant orogenital ulceration of Behçet's syndrome with infliximab. Rheumatology (Oxford). 2001. 40:473–474.